SMARCA4融合相关肉瘤的临床病理学及分子遗传学特征

Clinicpathological and molecular genetic features of SMARCA4-fusion associated sarcomas

目的探讨SMARCA4融合相关肉瘤的临床病理学及分子遗传学特征。方法回顾性分析2例SMARCA4融合相关肉瘤的临床病理学及免疫表型特征,采用二代测序技术分析分子遗传学特征。结果2例男童年龄分别为7岁(例1)及12岁(例2),病变部位为右侧睾丸及右侧腘窝,临床表现为右侧睾丸及右侧腘窝的无痛性占位,肿瘤最大径4.5~7.0 cm。镜检:低倍镜下2例瘤细胞均呈弥漫片状及交织束状排列,瘤细胞疏密不等,呈圆细胞样、上皮样及梭形,肿瘤性间质为黏液性及胶原样基质,均可见凝固性坏死,核分裂象均易见。例1以黏液样间质为主;例2以胶原化背景为主。免疫表型:2例具有肌源性分化,表达desmin和SMA;部分表达CD99;SMARCA2、SMARCA4(BRG1)、SMARCAB1(INI-1)、ARID1A、H3K27ME3表达均无缺失,Ki-67增殖指数分别为60%、20%。2例随访时间8~22个月,例1未见复发及转移,例2复发,出现可疑肺转移。2例均检测到SMARCA4融合,分别为SMARCA4-DOCK6融合及SMARCA4-VEZF1融合。结论SMARCA4融合相关肉瘤是一种罕见的恶性软组织肿瘤,分子特点为SMARCA4融合。

Purpose To investigate the clinicopathological and genetic features of SMARCA4-fusion associated sarcomas.Methods The clinical morphological and immunohistochemical features of 2 SMARCA4-fusion associated sarcomas were retrospectively analyzed,and the molecular genetic features of two cases of SMARCA4-fusion associated sarcoma were studied using next generation sequencing technique.Results There were 2 males,aged 7 years and 12 years respectively,tumor occurred in the right testicle and right popliteal space.Presenting symptoms were painless masses.The tumours ranged from 4.5 to 7.0 cm in greatest dimensions.Microscopically,tumors were composed of round,spindle or epithelioid shaped cells arranged in fascicles or diffuse growth pattern with hypocellular areas and hypercellular areas.The background of tumors was myxoid or collagenous.Marked mitotic activity and tumor necrosis were seen.The first case had prominent myxoid stroma,but the second had prominent collagenous stroma.Tumor cells expressed desmin,SMA,SMARCA2,SMARCA4(BRG1),SMARCAB1(INI-1)and ARID1A.Two cases also expressed CD99.Loss of nuclear H3K27ME3 expression was not observed,the Ki-67 index of tumor cells were 60%and 20%respectively.Follow up information was available in two cases,the first case had no recurrence and metastasis,the second had local recurrence and suspected lung metastases(range 8 to 22 months).SMARCA4 gene fusions were detected in 2 cases:a SMARCA4-DOCK6 fusion and a SMARCA4-VEZF1 fusion.Conclusion SMARCA4-fusion associated sarcomas is a rare malignant soft tissue tumor.Their genetic hallmark is the presence of SMARCA4 fusions.